Since the first attempts at the turn of the twentieth century, enormous progress has been made in the area of the chemical synthesis of O-glycosides. However, it was only in the past two decades that the scientific world had witnessed a dramatic improvement the methods used for chemical glycosylation. The development of new classes of glycosyl donors has not only allowed accessing novel types o...

The design of covalent inhibitors in glycoscience research is important for the development of chemical biology probes. Here we report the synthesis of a new carbocyclic mechanism-based covalent inhibitor of an α-glucosidase. The enzyme efficiently catalyzes its alkylation via either an allylic cation or a cationic transition state. We show this allylic covalent inhibitor has different catalyti...

a Cardiovascular Disease Service, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, MD, United States b Pulmonary Disease and Critical Care Service, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, MD, United States c Internal Medicine Service, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, MD, United ...

There is increasing evidence that cardiac glycosides act through mechanisms distinct from inhibition of the sodium pump but which may contribute to their cardiac actions. To more fully define differences between agents indicative of multiple sites of action, we studied changes in contractility and action potential (AP) configuration in cat ventricular myocytes produced by six cardiac glycosides...

A RECENT editorial in this journal 1 comments on the difficulty of establishing a physiological basis for the clinical, electrocardiographic, and hemodynamic effects of cardiac glycosides on the hearts of patients with heart disease. It is now accepted that heart muscle is not a syncytium, but consists, like other organs, of discrete cells.2 Accordingly, measurements of cardiac function reflect...

A RECENT editorial in this journal 1 comments on the difficulty of establishing a physiological basis for the clinical, electrocardiographic, and hemodynamic effects of cardiac glycosides on the hearts of patients with heart disease. It is now accepted that heart muscle is not a syncytium, but consists, like other organs, of discrete cells.2 Accordingly, measurements of cardiac function reflect...

Muscarinic potassium channels (KACh) are composed of two subunits, GIRK1 and GIRK4 (or CIR), and are directly gated by G proteins. We have identified a novel gating mechanism of KACh, independent of G-protein activation. This mechanism involved functional modification of KACh which required hydrolysis of physiological levels of intracellular ATP and was manifested by an increase in the channel ...

Digitalis is a genus of about 20 species of herbaceous perennials, shrubsand biennials commonly called foxgloves. The term digitalis is also used for drug preparations that contain cardiac glycosides, particularly the one called Digoxin, extracted from various plants of this genus. Cardiac glycosides cause arteriolar and venous constriction in a variety of mammalian species including human bein...

A RECENT editorial in this journal 1 comments on the difficulty of establishing a physiological basis for the clinical, electrocardiographic, and hemodynamic effects of cardiac glycosides on the hearts of patients with heart disease. It is now accepted that heart muscle is not a syncytium, but consists, like other organs, of discrete cells.2 Accordingly, measurements of cardiac function reflect...

A RECENT editorial in this journal 1 comments on the difficulty of establishing a physiological basis for the clinical, electrocardiographic, and hemodynamic effects of cardiac glycosides on the hearts of patients with heart disease. It is now accepted that heart muscle is not a syncytium, but consists, like other organs, of discrete cells.2 Accordingly, measurements of cardiac function reflect...